The Derived Neutrophil-to-Lymphocyte Ratio Is an Independent Prognostic Factor in Transplantation Ineligible Patients with Multiple Myeloma

Abstract

Background: The neutrophil-to-lymphocyte ratio (NLR) is an independent prognostic marker in solid and hematological cancers. While the derived NLR (dNLR) was shown to be non-inferior to the NLR in large cohorts of patients with different cancer types, it has not been validated as a prognostic marker for multiple myeloma (MM) to date. Methods: Between May 22, 2011 and May 29, 2014, 176 patients with MM from 38 centers who were ineligible for autologous stem cell transplantation were analyzed. The dNLR was calculated using complete blood count differential data. The optimal dNLR cut-off value according to receiver operating characteristic analysis of overall survival (OS) was 1.51. All patients were treated with melphalan and prednisone combined with bortezomib. Results: The complete response rate was lower in the high dNLR group compared to the low dNLR group (7 vs. 26.1%, respectively; p = 0.0148); the corresponding 2-year OS rates were 72.2 and 84.7%, respectively (p = 0.0354). A high dNLR was an independent poor prognostic factor for OS (hazard ratio 2.217, 95% CI 1.015–4.842; p = 0.0458). Conclusion: The dNLR is a readily available and cheaply obtained parameter in clinical studies, and shows considerable potential as a new prognostic marker for transplantation-ineligible patients with MM.

Enhanced piezoelectric, electrocaloric and energy storage properties at high temperature in lead-free Bi0.5(Na1-xKx)0.5TiO3 ceramics

“…For BNKT 10, the d 33 is increased from 100 pC/N at 20 o C to 125 pC/N at 165 o C, see in Figure 5 (b). Similar phenomena of increased d 33 have been observed in BiFeO 3 -based ceramic[14,44] and PZT5 ceramic[45]. The increased d 33 may be related to the non-180 domain switching induced by internal bias field due to low activation energy at rising temperature.…”

“…Ferroelectric materials are widely studied due to their applications in actuators [1]， piezoelectric sensors [2], ferroelectric memories [3], solid-states cooling [4] and energy storage devices [5,6], etc. In the recent years, the growing concerns of the toxicity of lead and environmental protection, lead-free BaTiO 3 (BT) [7], (K 0.5 Na 0.5 )NbO 3 (KNN) [8], (Bi 0.5 Na 0.5 )TiO 3 (BNT) [9][10][11][12][13]，BiFeO 3 (BFO) [14]-based materials are developed as alternatives for commercial Pb-based ceramics. Pure BNT ceramic exhibits rhombohedral R3c phase at room temperature with a high Curie temperature (T c~3 20 o C) and large remnant polarization (P r =38 /cm 2 ) as well as high coercive field (E c =73 kV/cm) [15].…”

High-density neutrophils in MGUS and multiple myeloma are dysfunctional and immune-suppressive due to increased STAT3 downstream signaling

“…The heat map indicates the relative abundance (red to blue) of the genes specifically Neutrophils are terminally differentiated cells which provide to eliminate microbial organisms by phagocytosis, release of cytotoxic granules or extracellular traps 13 , but can work as weak antigen-presenting cells regulating antigen-specific T-cell responses, as recently described 14,15 . Revealing the complex immunological dysregulation in MM, the neutrophil-to-lymphocyte ratio at diagnosis or after 100 days from autologous stem cell transplantation can predict outcome in MM patients, even if the novel agents era [16][17][18][19][20][21][22] In cancer, neutrophils can integrate the environmental signals towards an adaptive response to the tumor-associated sterile inflammation, generally associated to a pro-tumoral phenotype 13,[23][24][25][26] . Defects in neutrophil maturation, including reduced lysozyme activity 27 and increased expression of arginase 28,29 , have been described in MM as consequence of the infiltration of the bone marrow by neoplastic cells 27 , but little is known about the contribution of human HDNs in progression from MGUS to MM.…”

The (Neutrophils + Monocyte)/Lymphocyte Ratio Is an Independent Prognostic Factor for Progression-Free Survival in Newly Diagnosed Multiple Myeloma Patients Treated With BCD Regimen

“…Peripheral blood absolute lymphocyte count (ALC), absolute neutrophil count (ANC) and absolute monocyte count (AMC) have been used as good surrogate markers of immune surveillance in several solid tumors and hematologic malignancies including MM ( 23 – 26 ). In MM, ANC/ALC ratio (NLR) and ALC/AMC ratio (LMR) have been found to be independent prognostic factors at the time of diagnosis, before, and after autologous hematopoietic stem cell transplantation ( 13 , 17 – 19 , 22 ). Most of them concluded that elevated NLR and low LMR could predict poor prognosis.…”

“…Moreover, the success of CAR-T cells in MM treatment also showed that the recovery of patient’s immune function plays an important role in further improving the efficacy of treatment of MM ( 10 – 12 ). Therefore, the immunosuppressive state of MM patients at diagnosis may be an important reason to limit further improvement of the efficacy ( 13 , 14 ). How to evaluate the overall immune status of patients is an urgent problem in clinical practice.…”